development-novel-internal-fixation-model-for-rat-radial-fractures

Development of a Novel Internal Fixation Model for Rat Radial Fractures: Fracture Healing Assessment and Dorsal Root Ganglion Isolation

The rat radial fracture model is of significant importance in orthopedic research, particularly for studying fracture-healing mechanisms, drug screening, ...

The reasons for the relationship between depression and chronic liver disease (CLD) are complex and multifactorial. Further research is needed to decipher the etiology and establish an optimal management approach for depression in patients, including the potential role of non-pharmacological treatments. monosodium glutamate (MSG)-treated rats are more likely to develop anxiogenic- and depressive-like behaviors, which could be related to the dysfunction of serotonergic system. In this study, partial hepatectomy (PH) was performed in MSG-treated rats and the histopathological changes were observed in orbitofrontal cortex (OFC) and liver. The effect of escitalopram, a widely used antidepressant, on neural and liver injury in this model was also examined. The MSG + PH-treated rats displayed decreased distances traveled in total, in center arena, and in the left side of arena in inner open field test (OFT), as compared to saline, saline + PH, and MSG-treated animals. The present study established that PH aggravated anxiety-like depressive behaviors in MSG-treated rats, concordant with damaged Nissl bodies (and neurites), decreased IBA-1 and Sox-2 expression in OFC and neurotransmitter disorder. Escitalopram treatment could alleviate these pathological changes as well as reduce hepatic steatosis and lipid metabolism.

Preventive Effects of Escitalopram Against Anxiety-Like Depressive Behaviors in Monosodium Glutamate-Teated Rats Subjected to Partial Hepatectomy.

 Ulcerative colitis (UC) is an inflammatory bowel disease with a high incidence rate and a difficult treatment regimen. Recently, significant advances in the treatment of intestinal diseases, particularly UC, have been made with the use of the drugs baicalin and baicalein, separately or in combination. However, the therapeutic efficacy and mechanism of action of baicalin, baicalein, and their combination therapy, in the treatment of UC has not been fully elucidated.  we constructed a UC rat model that encompassed a variety of complex factors, including a high-sugar and high-fat diet, a high temperature and humidity environment (HTHE), excess drinking, and infection of . Model rats were then treated with baicalin, baicalein, or a combination of the two.  The results showed significant differences in the therapeutic effects of baicalin, baicalein, and the combination therapy, in the treatment of UC, as well as differences in the inhibition of inflammation  the nuclear factor-κB and MAPK pathways. The rat model of UC was established as described above. Then, the rats were treated for 7 days with baicalin (100 mg kg), baicalein (100 mg kg), or both (100 mg kg, baicalin: baicalein = 4:1/1:1). Clinical symptoms and signs, body temperature, organ indices, histopathology, blood biochemistry, and metabolites were examined to compare treatment effects and indicators of UC. Baicalin, YSR (Young  ratio of baicalin and baicalein), baicalein, and WSR (Withered  ratio of baicalin and baicalein) had significantly different effects in terms of clinical symptoms and signs, body temperature, organ indices, serum inflammatory cytokine levels, blood biochemistry, and histopathology changes in the main organs; YSR exhibited the best treatment effects. LC-MS/MS was used to detect the conversion of baicalin, baicalein, or both, into the six types of metabolites: baicalin, wogonoside, oroxin A, baicalein, wogonin, and oroxylin A. The levels of the six metabolites under the different treatment conditions were significantly different in the large intestine, small intestine, and lungs, but not in the blood. The levels of the six metabolites were significantly different in the large intestine, small intestine, and lung, but not in the serum.  All these results indicate that baicalin and baicalein should be used more accurately in specific diseases, especially baicalin or high content of baicalin in  (Tiaoqin) should be preferred in treatment of UC.

The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat.

Skeletal muscle atrophy is an important feature of cancer cachexia, which can be induced by chemotherapy, and affects the survival and quality of life of cancer patients seriously. No specific drugs for cancer cachexia have been applied in clinical practice. This study explored the therapeutic effect of linalool (LIN) on cisplatin (DDP) induced skeletal muscle atrophy. , LIN can improve skeletal muscle weight loss, anorexia, muscle strength decline and other cachexia symptoms caused by cisplatin treatment in a Lewis lung cancer tumor bearing mouse model, and cause no adverse effects on the anti-tumour effect. LIN treatment decreased the expression of muscle RING-finger protein-1 (MuRF1) and Atrogin1(MAFbx) in muscle, and the activation of insulin-like growth factor-1 (IGF-1)/protein kinase B (Akt)/forkhead box O (FoxO) pathway was observed. , LIN alleviated DDP induced C2C12 myotube atrophy, and IGF-1 receptor inhibitor Picropodophyllin (PIC), which had no adverse effect on C2C12 myotube cells, could reverse the protective effect of LIN. These results indicate that LIN down-regulates the expression of Atrogin1 and MuRF1 through the IGF-1/Akt/FoxO pathway, alleviating DDP-induced muscle atrophy and improving cachexia symptoms. LIN has the potential to be developed as a drug against cancer cachexia.

Linalool Prevents Cisplatin Induced Muscle Atrophy by Regulating IGF-1/Akt/FoxO Pathway.

Liver injury caused by acetaminophen (AP) overdose is a leading public health problem. Although AP-induced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone (NAPQI), a toxic metabolite of AP, resulting in cell damage, emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota. However, the gut microbiota-involved mechanism remains largely unknown. In our study, we found that vancomycin (Vac) pretreatment (100 mg/kg, twice a day for 4 days) attenuated AP-induced liver injury, altered the composition of gut microbiota, and changed serum metabolic profile. Moreover, we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid (2-HB), which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels. Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.

Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid.

Aberrant expression of serine/arginine-rich splicing factor 2 (SRSF2) can lead to tumorigenesis, but its molecular mechanism in colorectal cancer is currently unknown. Herein, we found SRSF2 to be highly expressed in human colorectal cancer (CRC) samples compared with normal tissues. Both in vitro and in vivo, SRSF2 significantly accelerated the proliferation of colon cancer cells. Using RNA-seq, we screened and identified 33 alternative splicing events regulated by SRSF2. Knockdown of SLMAP-L or CETN3-S splice isoform could suppress the growth of colon cancer cells, predicting their role in malignant proliferation of colon cancer cells. Mechanistically, the in vivo crosslinking immunoprecipitation assay demonstrated the direct binding of the RNA recognition motif of SRSF2 protein to SLMAP and CETN3 pre-mRNAs. SRSF2 activated the inclusion of SLMAP alternative exon 24 by binding to constitutive exon 25, while SRSF2 facilitated the exclusion of CETN3 alternative exon 5 by binding to neighboring exon 6. Knockdown of SRSF2, its splicing targets SLMAP-L, or CETN3-S caused colon cancer cells to arrest in G1 phase of the cell cycle. Rescue of SLMAP-L or CETN3-S splice isoform in SRSF2 knockdown colon cancer cells could effectively reverse the inhibition of cell proliferation by SRSF2 knockdown through mediating cell cycle progression. Importantly, the percentage of SLMAP exon 24 inclusion increased and CETN3 exon 5 inclusion decreased in CRC samples compared to paired normal samples. Collectively, our findings identify that SRSF2 dysregulates colorectal carcinoma proliferation at the molecular level of splicing regulation and reveal potential splicing targets in CRC patients.

Comprehensive analysis of RNA-binding protein SRSF2-dependent alternative splicing signature in malignant proliferation of colorectal carcinoma.

 Polysaccharides are important components of Panax notoginseng that contribute to its immunomodulatory ability. This study aimed to isolate polysaccharides from notoginseng and investigate the structural feature and potential immunomodulatory activity.  The polysaccharide was isolated from notoginseng by anion exchange and gel permeation chromatography. Its preliminary structure was characterized by Fourier transform infrared (FT-IR) spectroscopy, gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. The immunoregulatory function was further investigated in cyclophosphamide induced immunosuppressive mice, murine splenocytes and macrophages.  A novel homogeneous polysaccharide (PNPB1) was isolated from notoginseng with the molecular weight of 9.3 × 10 Da. Monosaccharide composition analysis indicated that PNPB1 consisted of Glc (88.2%), Gal (9.0%), Ara (2.4%) and trace GlcA, with the major backbone of (1→4)-linked α-Glcp, (1→6)-linked β-Glcp, and (1, 4→6)-linked β-Glcp. The polysaccharide was found to significantly enhance murine body weight, improve their thymus and spleen indices and increase the white blood cells (WBC). PNPB1 significantly enhanced splenic lymphocyte proliferation, NO and cytokine (TNF-α, IL-2, IL-10 and IFN-γ) production, as well as the phagocytosis and TLR2 expression of peritoneal macrophages, indicating potent immunoenhancement effect.  These findings provide a theoretical basis for elucidating the structure and immune activity of notoginseng polysaccharides.

Structural characterization and immunomodulatory activity of a novel polysaccharide from .

 Although β-catenin is frequently activated in various cancers, no targeted therapies have been approved for clinical use.  High-throughput drug screening was performed to identify potential compounds against β-catenin-activated tumors. The efficacy of identified compounds was assessed in orthotopic β-catenin-driven hepatocellular carcinoma model mice.  OSI-027 emerged as the most potent agent that selectively inhibited β-catenin-mutant cells. Mechanistically, β-catenin enhanced the transcription of Cofilin 1 (CFL1), a key stimulator of macropinocytosis, and directly interacted with CFL1 to prevent its inactivation. OSI-027 induced macropinocytosis and subsequently led to methuosis-like cell death of β-catenin-mutant cells. Moreover, both excessive macropinocytosis induced by OSI-027 and macropinocytosis inhibition via CFL1 depletion suppressed β-catenin-driven tumor growth in orthotopic hepatocellular carcinoma model mice.  Targeting macropinocytosis represents a promising therapeutic strategy for β-catenin mutant cancers.

Oncogenic β-catenin stimulation of cofilin 1-mediated macropinocytosis is druggable for cancer.

China bears the highest global burden of obstructive sleep apnea (OSA), yet its spatiotemporal and occupational patterns remain unclear. We quantified OSA prevalence across Chinese subpopulations, focusing on geographic disparities, temporal trends, and occupational risks.

Spatiotemporal Trends in the Prevalence of Obstructive Sleep Apnoea Across China: A Multilevel Meta-Analysis Incorporating Geographic and Demographic Stratification (2000-2024).

Proanthocyanidins play a crucial role in celiac disease (CD) through their antioxidant and anti-inflammatory properties, effectively regulating oxidative stress and inflammatory responses. However, the poor stability and low bioavailability of proanthocyanidins significantly limit their therapeutic applications. The aim of this study was to investigate the effects of lyoprotectants on proanthocyanidin nanoliposome freeze-dried powder (PCNL-FD), characterize its structural properties, evaluate its in vitro antioxidant capacity and explore its protective effects in a celiac disease cell model. The addition of 4% trehalose as a lyoprotectant effectively maintained the encapsulation efficiency and redispersion stability of PCNL-FD. FTIR and TEM analyses confirmed the successful incorporation of proanthocyanidins into the phospholipid bilayer. In vitro antioxidant assays showed that PCNL-FD exhibited significantly higher DPPH, ABTS, and hydroxyl radical scavenging activities compared to free proanthocyanidins. In the p31-43 peptide-induced celiac disease Caco-2 cell model, PCNL-FD significantly reduced oxidative stress by decreasing ROS and MDA levels while increasing GSH levels and antioxidant enzyme activities (SOD and CAT). The formulation showed anti-inflammatory effects by inhibiting pro-inflammatory cytokines (TNF-α, IL-6) and promoting anti-inflammatory cytokines (IL-4, IL-10). In addition, PCNL-FD activated the Keap1/Nrf2 signaling pathway and upregulated the expression of NQO-1 and HO-1. This nanoliposomal delivery system effectively overcame the bioavailability and stability limitations of free proanthocyanidins, providing new insights into the management of oxidative stress in inflammatory diseases such as celiac disease.

Protective Effects Proanthocyanidin Nanoliposome Freeze-Dried Powder on Oxidative Injury in a p31-43 Induced Celiac Disease Cell Model.

Heterogeneous nuclear ribonucleoprotein M (hnRNPM) is an RNA-binding protein that is aberrantly expressed in tumorigenesis. However, the alternative splicing regulation by hnRNPM in human colorectal cancer (CRC) remain unclear. Herein, we observed that hnRNPM was highly expressed in CRC tissues. The knockdown of hnRNPM inhibited the proliferation of colon cancer cells both in vivo and in vitro. Using RNA-seq, we screened and identified several alternative splicing events regulated by hnRNPM. Knockdown of PLEKHB2-S splice isoform could reduce the growth of colon cancer cells in vitro and in vivo, predicting its role in malignant proliferation of colon cancer cells. Mechanically, the minigene reporter assay indicated the predominant regulatory roles of hnRNPM in PLEKHB2 splicing. The in vivo crosslinking immunoprecipitation (CLIP) assay demonstrated the direct binding of the RNA recognition motif RRM2 of hnRNPM protein to exon 9 of PLEKHB2 pre-mRNA. HnRNPM facilitated the skipping of alternative exon 8 in PLEKHB2 by binding to the constitutive exon 9. Furthermore, we developed cationic microbubbles shRNA/CMBs and transferred to colon cancer cells via ultrasound-targeted microbubble disruption (UTMD). The size and zeta potentials of CMBs and shRNA-CMBs were measured and the optimal concentration range of shRNA/CMBs were screened with low cytotoxicity. The introduction of sh-hnRNPM/CMBs or sh-PLEKHB2-S/CMBs suppressed the proliferation of colon cancer cells in vitro and in vivo. Collectively, our findings identify that hnRNPM dysregulates colorectal carcinoma proliferation at the molecular level of splicing regulation and predicate sh-hnRNPM/CMBs and its splicing target sh-PLEKHB2-S/CMBs as promising therapeutic drugs and innovative strategies for treating colorectal cancer. Schematic diagram of the functions of UTMD mediated sh-hnRNPM/CMBs in colorectal cancer and emerging mechanism by which hnRNPM promotes the malignant proliferation of CRC by regulating the alternative splicing of PLEKHB2 pre-mRNA. The picture was created with BioRender.com.

Emerging roles of RNA-binding protein hnRNPM in alternative splicing regulation and UTMD mediated sh-hnRNPM/CMBs suppress the proliferation of colorectal cancer.

Article	Year
Preventive Effects of Escitalopram Against Anxiety-Like Depressive Behaviors in Monosodium Glutamate-Teated Rats Subjected to Partial Hepatectomy. Frontiers in psychology\| PubMed ID: 31798487	2019
The Comparative Study of the Therapeutic Effects and Mechanism of Baicalin, Baicalein, and Their Combination on Ulcerative Colitis Rat. Frontiers in pharmacology\| PubMed ID: 31920656	2019
Linalool Prevents Cisplatin Induced Muscle Atrophy by Regulating IGF-1/Akt/FoxO Pathway. Frontiers in pharmacology\| PubMed ID: 33390985	2020
Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid. Journal of pharmaceutical analysis\| PubMed ID: 33425450	2020
Comprehensive analysis of RNA-binding protein SRSF2-dependent alternative splicing signature in malignant proliferation of colorectal carcinoma. The Journal of biological chemistry\| PubMed ID: 36623729	2023
Structural characterization and immunomodulatory activity of a novel polysaccharide from . Frontiers in pharmacology\| PubMed ID: 37256230	2023
Oncogenic β-catenin stimulation of cofilin 1-mediated macropinocytosis is druggable for cancer. Theranostics\| PubMed ID: 40213667	2025
Spatiotemporal Trends in the Prevalence of Obstructive Sleep Apnoea Across China: A Multilevel Meta-Analysis Incorporating Geographic and Demographic Stratification (2000-2024). Nature and science of sleep\| PubMed ID: 40370656	2025
Protective Effects Proanthocyanidin Nanoliposome Freeze-Dried Powder on Oxidative Injury in a p31-43 Induced Celiac Disease Cell Model. Food science & nutrition\| PubMed ID: 41019173	2025
Emerging roles of RNA-binding protein hnRNPM in alternative splicing regulation and UTMD mediated sh-hnRNPM/CMBs suppress the proliferation of colorectal cancer. Oncogene\| PubMed ID: 41109930	2025

Linlin Chen

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